Prenatal programming of neuroendocrine reproductive function

It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the “prenatal programming” of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be “shaped” both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent “normal function”. The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on reproductive potential

Clothes and how to care for them

Cooperative Extension Work in Agriculture and Home Economics, University of Missouri, College of Agriculture and the United States Department of Agriculture cooperating."March, 1937 (Fourth Edition)."Title from cover

Motor development research : I. The lessons of history revisited (the 18th to the 20th century)

In 1989, Clark and Whitall asked the question “What is motor development”. They were referring to the study of motor development as an academic research enterprise and answered their question primarily by describing four relatively distinct time periods characterized by changes in focus, theories or concepts and methodology. Their last period was named the process-oriented period (1970-1989). In hindsight, it seems clear that their last period could be divided into two separate historical time periods: the information-processing period (1970-1982) and the dynamical systems period (1982-2000). In the present paper, we briefly revisit the first three periods defined by Clark and Whitall, and expand and elaborate on the two periods from 1970 to the turn of the century. Each period is delineated by key papers and the major changes in focus, theories or concepts and methodology. Major findings about motor development are also described from some papers as a means of showing the progression of knowledge

Enabling Performance-Based Navigation Arrivals: Development and Simulation Testing of the Terminal Sequencing and Spacing System

NASA has developed an advanced arrival management capability for terminal controllers, known as Terminal Sequencing and Spacing (TSS). TSS increases use of performance-based navigation (PBN) arrival procedures during periods of high traffic demand. It extends two Federal Aviation Administration's operational systems with terminal metering and controller spacing tools. Sixteen high-fidelity human-in-the-loop simulations, involving more than five hundred hours of evaluation time, were conducted to mature TSS from proof-of- concept design to fully functional prototype. These simulations modeled arrival procedures at several U.S. airports, incorporated a broad range of traffic demand profiles and wind conditions, and used controllers with extensive operational experience. Two fundamental metrics are evaluated for these simulations: PBN Success Rate and Inter-Arrival Spacing Error. The PBN Success Rate shows a definitive trend when TSS is used. It increases from 42 percent for today's operations to 68 percent for terminal metering only and 92 percent for terminal metering with controller-managed spacing tools. Meanwhile, the Inter-Arrival Spacing Error improves 25 to 35 percent when TSS is used compared to not used. The TSS technology was transferred to the FAA and, and it is targeted for deployment to several busy airports in the U.S. starting in 2018

Health Care Seeking Behavior among Caregivers of Sick Children Who Had Cerebral Malaria in Northwestern Nigeria

Cerebral malaria is a significant cause of childhood morbidity in our region. The challenges of effective management include time and quality of treatment. The study appraised the health care seeking behavior of caregivers of sick children who developed cerebral malaria, in Zaria, northwestern Nigeria. Caregivers indentified were parents 29 (87.9%) and grandparents 4 (12.1%). Most of them were in the upper social classes. Health care options utilized before presentation at our facility were formal health facility 24 (72.7%), patent medicine seller 12 (36.4%), home treatment 10 (30.3%), and herbal concoction 6 (18.2%) with majority 24 (72.7%) using more than one option. Antimalarial therapy was instituted in 25 (75.6%) of the cases. Mortality was significantly associated with the use of herbal concoction, treatment at a formal health facility and patent medicine seller, multiple convulsions, age less than 5 years, and noninstitution of antimalarial therapy before presentation. The study showed use of inappropriate health care options by caregivers and highlighted the need to pursue an awareness drive among caregivers on the use of health care options

GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity.

Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype. Time-lapse confocal imaging of tumor cells in brain slice cultures demonstrated blood vessel co-option by tumor cells and highlighted differences in invasive pattern. Inhibition of EGFR signaling in pEGFRHi promoted cell differentiation and increased cell-matrix adhesion. Conversely, increased EGFRvIII activation in pEGFRLo reduced cell-matrix adhesion. Our study using a murine model for GBM driven by a single genetic driver, suggests differences in EGFR activation contribute to tumor heterogeneity and aggressiveness

Prenatal Exposure of the Ovine Fetus to Androgens Sexually Differentiates the Steroid Feedback Mechanisms That Control Gonadotropin Releasing Hormone Secretion and Disrupts Ovarian Cycles

Exposure of the female sheep fetus to exogenous testosterone in early pregnancy permanently masculinizes the reproductive neuroendocrine axis. Specifically, in utero androgens given to female lambs from day 30 to 90 of a 147 day pregnancy dramatically altered the response of the gonadotropin releasing hormone (GnRH) neuronal network in the hypothalamus to both estrogen (E) and progesterone (P) feedback. Elevated concentrations of estrogen stimulated a massive release of GnRH in gonadectomized female sheep; however, male and androgenized female lambs were unable to respond to high E concentrations by producing this preovulatory-like “surge” of GnRH. Further, the inhibitory actions of progesterone (P) were also sexually differentiated and adult males and androgenized females were much less responsive to P-negative feedback than normal ewes. The consequences of these abnormal steroid feedback mechanisms were reflected in the fact that only 72% of ovary-intact androgenized ewes exhibited normal estrous cycles in their first breeding season whereas none had a single estrous cycle during the second breeding season. In contrast, 100% of the control animals exhibited repeated reproductive cycles in both seasons. These data indicate that a relatively short exposure to male hormones during in utero life permanently alters the neural mechanisms that control reproduction and leads progressively to a state of infertility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44102/1/10508_2004_Article_365183.pd

Dose-response effects of light at night on the reproductive physiology of great tits (Parus major): integrating morphological analyses with candidate gene expression

Artificial light at night (ALAN) is increasingly recognized as a potential threat to wildlife and ecosystem health. Among the ecological effects of ALAN, changes in reproductive timing are frequently reported, but the mechanisms underlying this relationship are still poorly understood. Here, we experimentally investigated these mechanisms by assessing dose‐dependent photoperiodic responses to ALAN in the great tit (Parus major). We individually exposed photosensitive male birds to one of three nocturnal light levels (0.5, 1.5, and 5 lux), or to a dark control. Subsequent histological and molecular analyses on their testes indicated a dose‐dependent reproductive response to ALAN. Specifically, different stages of gonadal growth were activated after exposure to different levels of light at night. mRNA transcript levels of genes linked to the development of germ cells (stra8 and spo11) were increased under 0.5 lux compared to the dark control. The 0.5 and 1.5 lux groups showed slight increases in testis size and transcript levels associated with steroid synthesis (lhr and hsd3b1) and spermatogenesis (fshr, wt1, sox9, and cldn11), although spermatogenesis was not detected in histological analysis. In contrast, all birds under 5 lux had 10 to 30 times larger testes than birds in all other groups, with a parallel strong increase in mRNA transcript levels and clear signs of spermatogenesis. Across treatments, the volume of the testes was generally a good predictor of testicular transcript levels. Overall, our findings indicate that even small changes in nocturnal light intensity can increase, or decrease, effects on the reproductive physiology of wild organisms

Reflections on motor development research across the 20th century : six empirical studies that changed the field

Motor development research has had a rich history over the 20th century with a wide array of scientists contributing to a broad and deep body of literature. Just like the process of development, progress within the field has been non-linear, with rapid periods of growth occurring after the publication of key research articles that changed how we conceptualized and explored motor development. These publications provided new ways to consider developmental issues and, as a result, ignited change in our theoretical and empirical approaches within the field of motor development and the broader field of developmental psychology. In this paper, we outline and discuss six pioneering studies that we consider significant in their impact and in the field's evolution, in order of publication: Halverson, 1931; Wild, 1938; Gibson & Walk, 1960; Connolly, Brown, & Bassett, 1968; Thelen & Fisher, 1982; Thelen & Ulrich, 1991. We have limited this review to empirical papers only. Together, they offer insight into what motor development research is, where it came from, why it matters, and what it has achieved